# Chromosomal Boundary Alterations Driving Transcriptional Dysregulation in Brain Disorders

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $453,801

## Abstract

PROJECT ABSTRACT
Many genetic disorders are characterized by defects in neuronal function and cognitive ability. To gain
key insights into new ways of approaching these diseases, it is critical to understand the molecular
basis for regulating neuronal transcriptional programs and take advantage of emerging global
genomic technologies, which provide deep insights into the molecular basis for these disorders. Here,
we focus on a severe neurological disorder that is caused by mutations of the methyl-CpG-binding
protein, MeCP2, and how it causes alterations in gene expression programs required for neuronal
function. We propose to investigate this perplexing syndrome, which can be categorized under the
umbrella of “autism spectrum” disorders, to test a previously unappreciated mechanism for regulating
neuronal transcription programs based on chromosomal architecture. Specifically, we will determine
the effects of MeCP2 loss on chromatin architecture and its relation to changes in gene transcription,
as well as determine the functional role of MeCP2 on the nuclear matrix-dependent architectural
network. We will utilize several mouse genetic models to target several important brain cell types and
apply genome wide methodologies to elucidate the contribution of each of these to the observed brain
phenotype. We expect to expand our understanding of MeCP2-dependent transcriptional de-
regulation due to structural effects on chromosome architecture, and uncover the role of MeCP2 in
regulation of chromosomal boundary/ sub-nuclear architectural interactions as an underlying
mechanism in Rett syndrome. This will enable new understanding of the molecular mechanisms of
this devastating neurological disease, and lay the groundwork for potential new classes of potential
therapeutic avenues.

## Key facts

- **NIH application ID:** 9930679
- **Project number:** 5R01NS093066-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** MICHAEL G ROSENFELD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $453,801
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930679

## Citation

> US National Institutes of Health, RePORTER application 9930679, Chromosomal Boundary Alterations Driving Transcriptional Dysregulation in Brain Disorders (5R01NS093066-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9930679. Licensed CC0.

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